Association of lipoprotein(a) with all-cause and cause-specific mortality: A prospective cohort study

Background: A growing number of studies have demonstrated a causal association between lipoprotein(a) [Lp(a)] and atherosclerotic cardiovascular diseases (ASCVDs), but its association with all-cause and cause-specific mortality remains unclear. Therefore, this study aimed to explore the association of Lp(a) with all-cause and cause-specific mortality. Methods: This prospective cohort study included 8,525 participants from the third National Health and Nutrition Examination Survey. Lp(a) was considered an exposure variable, all-cause and cause-specific mortality were used as outcome variables, and all participants were followed from the interview date until death or December 31, 2015. COX proportional hazards regression models, stratified analysis, sensitivity analysis, restricted cubic spline plots and Kaplan-Meier survival curves were used to analyze the association of Lp(a) with all-cause and cause -specific mortality. Results: After adjusting for traditional cardiovascular risk factors, Lp(a) remained strongly associated with all -cause and CVDs-related mortality (P for trend = 0.007 and < 0.001). Subgroup analyses showed that higher Lp(a) remained associated with higher risk of all-cause mortality in those > 60 years of age, with a BMI < 30 kg/ m2, and without diabetes, whereas the association between Lp(a) and CVDs-related mortality remained stable in participants <= 60 years of age, male, with a BMI < 30 kg/m2, with hypertension, without diabetes, or without CVDs (P < 0.05). In sensitivity analyses, we found that the association of Lp(a) with all-cause and CVDs-related mortality remained robust after excluding individuals who died within one year of follow-up (P for trend = 0.041 and 0.002). Conclusions: Lp(a) was associated with the risk of all-cause and CVDs-related mortality.